The invention relates generally to biological tissue welding, and more specifically to repairing a lesion to a solid visceral organ. The invention also relates to manufacturing biocompatible albumin lamina suitable for use as a scaffold or patch in the repair of tissue of a solid visceral organ.
Solid visceral organs such as the liver, spleen and kidney have a soft parenchyma richly interspersed with vasculature and thinly protected by a delicate fibrous capsule with limited internal fibrous support. This structure makes such organs prone to fracture and laceration with blunt abdominal trauma. Such organs are also frequently injured following abdominal trauma. For example, the liver is the most commonly injured organ following abdominal trauma. It is the second most commonly injured following blunt injuries and the third most commonly injured in penetrating injuries.
Surgery of solid visceral organs like liver, spleen and kidney have always proved to be challenging, as these organs bleed profusely if traumatized and hold sutures rather poorly. Exsanguinating hemorrhage remains a significant cause of immediate mortality. A 3 cm parenchymal depth laceration has a 19% mortality and a parenchymal disruption involving 25-50% of a hepatic lobe has 28% mortality.
Few intra-abdominal injuries are as technically demanding as a major liver laceration. Such wounds require erudite judgment and innovative surgical techniques to prevent intraoperative exsanguination accelerated in some cases by hemodilution and coagulopathy. Conventional suture repair of major hepatic trauma additionally has a delayed morbidity and mortality from septicemia, peritonitis, biliary fistulae, and delayed intra-abdominal hemorrhage.
The current surgical armamentarium for liver lacerations is limited to mass ligation of the lacerated liver with absorbable sutures, omental wrapping, packing with re-exploration, mesh hepatorrhaphy, fibrin sealant and ultrasonic aspiration with argon beam coagulation. Suture repair of the liver frequently increases, parenchymal damage and ischemic tissue loss. Packing can be complicated by persistent hemorrhage and/or abdominal compartment syndrome and requires re-exploration to remove the packing. Biliary fistula and abscess formation can also complicate this technique. These difficulties also arise in repairing lesions in the kidney and spleen. They also present an obstacle to surgical treatment of solid visceral organs, for example, excision of tumors.
The use of lasers alone to control hemorrhage in the liver has had limited success in the past Tissue coagulation is the method of heating to denaturation the constituents of the tissue itself. Attempts at hemostasis using the CO2 laser have failed to show significant benefit when compared to the diathermy. Other work showed that the CO2 laser is ineffective at sealing vessels larger than 1 mm and that argon and Nd:YAG lasers are ineffective at stopping flow in vessels larger than 4.5 mm. These lasers achieve hemostasis by extensive (5-10 mm depth) thermal coagulation of proteins, causing major collateral tissue damage.
The use of laser energy to join tissue by heating a protein solder, typically albumin, is referred to as tissue welding. Laser soldering has been employed as an alternative to suture repair of injured tissues. Laser soldering was first utilized to anastomose rat ureters. Incorporating albumin solder into laser repairs was found to aid in controlling hemorrhage.
Solder are generally viscous liquids of biocompatible compositions. A representative composition is that of U.S. Pat. No. 5,292 362 (to Bass et al.), which discloses a liquid solder of collagen or albumin. Liquidity permits the solder to be easily applied and formed to the lesion, while its concentration serves to retain the solder at the applied site until irradiated. The highest viscosity of albumin readily producible corresponds to a 55-57% aqueous solution, enabling higher tensile strength weld joints. However, this albumin solder solution has the approximate consistency of honey. Higher concentrations of albumin, i.e., above 58%, dehydrate rapidly and cannot be freely handled in air.
It was recognized that adding a light-absorbing chromophore to the solder would increase and localize the absorption of energy to the solder level, thereby reducing both the amount of laser light required and collateral tissue damage. A chromophore is utilized to increase and localize the absorption of energy. The selection of chromophore also drives the choice of laser energy to be applied. For example, by using indocyanine green (ICG) as the exogenous chromophore, a diode laser could be operated at 800 nm. These lasers have the advantage of being relatively inexpensive. Further, their near-infrared light is poorly absorbed by solid visceral organ tissue, substantially mitigating thermal damage during a laser repair. Lastly, the specific absorption of energy by the chromophore pinpoints the heat generation locus to the solder layer. Reducing the amount of laser light required for solder activation permits lower laser energy settings. More efficient energy absorption also allows the use of pulsed lasers, further reducing collateral thermal damage during laser repairs.
Tissue welding using only an ICG-augmented albumin solder confers no advantage in some scenarios. Soldering can be employed to achieve hemostasis of severed liver venous sinusoids of larger diameters (i.e., 5 mm and above). However, the weld joints produced are brittle and of relatively low tensile strength. Previous repairs focus on nerve, ureter and vesicular and usually further include stay sutures. Solid visceral organs require a support contribution from the repair material. Solders exhibit low tensile strength and are not well-suited to provide this support. To date, laser soldering applications have not shown a clear benefit over conventional suture repair, and have not gained clinical acceptance
Mechanical considerations also militate against effecting lesion repair with irradiated liquid solder. Welding liver requires the application of an ICG-doped albumin solution to the weld area. As the ICG absorbs the laser light energy, the amount of ICG present (e.g., the thickness of the applied solution) is a significant factor in weld success and duplication. The non-uniformity in the albumin layer thickness during tissue repair is currently the greatest source of variability in laser repair using albumin solder.
Blood, bile and other fluids routinely exude from lesions. During laser solder repair, this seepage displaces the liquid solder from the surface of the damaged organ. Because of its viscosity, liquid solders cannot easily be manipulated to regain contact with the lesion site, instead necessitating deposit of further solder material and/or exposure of the lesion to additional energy. Alternatively, the fluids are irradiated and/or trapped beneath the welded solder material. Such entrapped weld joint contaminants adversely affect joint quality, strength and durability.
Laser soldering alone is also suboptimal for the repair of resecting injuries to solid visceral organs. Satisfactory repair of raw surface lesions is typically obtained with folding of the tissue or the application of some sort of a supportive film, described below. In addition to its bond strength, laying down and irradiating an uneven solder cover is likely to produce thinner, weaker points in the tissue weld. The longevity of repairs of raw surface traumas using only liquid solder is therefore suspect.
Efforts have also been made to repair damage to nerves and small vessels using solid welding patches, Such as Small pieces of dried albumin (1xc3x973xc3x970.5 mm strips). Further, such strips possess a low tensile strength, making them unsuitable for gross repairs such as resection or blunt trauma injuries. Lastly, these materials have been employed to repair nerves, ureters and other vessels. A need exists to direct the method of tissue welding to tissues possessing soft parenchyma, such as the liver, kidney and other solid visceral organs.
Solid biocompatible materials have been employed to repair injuries to tissues needing greater structural support than is offered by solder alone. Compositions include gelatin (U.S. Pat. No. 5,931,165 to Reich et al.); elastin (U.S. Pat. No. 6,110,212 to Gregory, et al.); and collagen (U.S. Pat. No. 5,749,895 to Sawyer et al.). Sawyer et al. teach making and using a sheet preferably made of collagen. The reference also mentions albumin as one of a number of alternative candidate materials. However, Sawyer et al. provide no description of the manufacture, method of use or physical characteristics of an albumin film. Further, none of the prior art references describe using an albumin film in the repair of injuries to solid visceral organs, such as liver, kidney and spleen.
Different methods have been attempted by Applicant to produce useful thin films of albumin. Prior efforts to extrude 55-57% albumin failed, as the solution would re-congeal upon exiting the extrusion orifice. Consequently, a need exists for a stable, pliable albumin lamina.
Applicant has experimented with welding liver lesions in liver by the application of ICG-doped liquid albumin solder to the weld area. As it is the ICG that absorbs the laser light energy, the thickness of the applied solution is a critical factor in weld success and repeatability. To date, this variable has not been controllable and the need for accurate and uniform albumin application persists. The albumin lamina of the present invention addresses this need by focusing on the preparation of thin albumin films, providing for the application of albumin of uniform and consistent thickness to a weld site.
Applications of energy to living tissue have the additional drawback of thermal damage to the lesion site under repair. The degree of damage varies according to the energy type and the amount applied, but can in some cases be substantial. In tissue coagulation, for example, the tissue is literally melted and then fused. An argon ion beam coagulator, used in this procedure, produces damage penetrating 3-4 mm into the tissue. While this repair technique seals the surface over an incision, superficial injury is sustained by the organ parenchyma well beyond the precise area of the incisive trauma. Such thermal damage also increases the risk of improper healing, spawning fistulae and other unwanted post-procedural complications. While thermal damage is more limited in soldering, a need exists to further minimize and control damage to healthy tissue surrounding or adjacent to a lesion in a locus of repair.
The present invention relates to the use of laser welding techniques on liver, kidney and spleenxe2x80x94solid tissues that are notoriously difficult to repair with sutures. Applicant""s experimental efforts achieved rapid hemostasis of in vivo liver lacerations (10 cm long and 1 cm deep) and lobar resections (5 by 2 cm) in swine. However, an integral part of the success of the swine experiments was the use of the pig""s omentum as a welding patch. A piece of the omentum was harvested during the procedure and placed over albumin-ICG solder. The omentum was then welded to the liver. Due to its transparent nature, the omentum let nearly 100% of the laser energy pass through and a strong weld occurred. The omentum thus served successfully as a hemostatic patch, reinforcing the albumin solder.
Successes with pig omentum could not be translated directly to humans, however. Native porcine omentum cannot be implanted in humans. On the other hand, human omentum is fatty and opaque, unlike the pig omentum. Therefore, rather than transmitting nearly all the laser energy, human omentum scatters a considerable amount, making it difficult to weld human omentum to tissue.
With this in mind, an albumin patch according to the present invention was developed which transmits 90% of incident laser energy. Being composed of albumin, the patch forms a strong bond with liquid albumin solder. Though not as strong a weld as those using omentum, the patch provided significant reinforcement to the weld site. Using the albumin lamina material provides substantially greater weld strength than solder alone.
The present invention provides a denatured albumin lamina, useful for repairing lesions on solid visceral organs. The lamina comprises human serum albumin, formed into a thin, pliant sheet and denatured. The denatured lamina can be sterilized and stored until used. As well, it can be impregnated with a variety of bioagents. Its mechanical properties make it especially suitable for use in tissue welding on solid visceral organs.
In another aspect of the present invention, a method is provided for manufacturing the denatured albumin lamina. The method comprises placing a quantity of viscous albumin solution between two nonporous sheets, then spreading the albumin solution between the sheets to a selected and substantially uniform thickness. The albumin solution sandwich is thus formed is placed into a container, which is then evacuated. The sandwich is then heated, by autoclaving or immersion in a water bath of at least 86xc2x0 C. Denaturation of the entrapped albumin solution changes its state from a viscous liquid to a flexible solid.
Another aspect of the present invention is a method for using the albumin lamina according to the present invention to repair a lesion on a solid visceral organ. The method comprises welding the albumin lamina over a lesion on a solid visceral organ. A laser solder is deployed beneath the lamina to weld it to the organ surface. In alternative embodiments, the albumin lamina is produced with additives in the form of bio-active agents.